Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking was significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African-American sample. Some drinking measures averaged across pregnancy may have under-estimated consumption and overestimated risk of SAb, but other risk drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk level alcohol consumption and protect from pregnancy loss.

Background: Fetal alcohol spectrum disorders (FASD), which are caused by prenatal alcohol exposure (PAE), affects people around the world. Certain communities in South Africa have among the highest reported incidences of fetal alcohol syndrome (FAS) in the world. Although PAE-related brain alterations have been widely documented, the mechanisms whereby alcohol affects the brain are not clearly understood. MRI relaxation parameters T1, T2, T2* and proton density (PD), are basic tissue properties that reflect the underlying biology. The present study aims to advance our understanding of how PAE alters the microstructural properties of tissue by examining PAE-related changes in these tissue parameters in adolescents with FASD. Methods: The final sample used in this study consisted of 53 children from a previously studied longitudinal cohort (Jacobson et al., 2008) and 12 additionally recruited subjects. Of the 65 participants, 18 were diagnosed with FAS or partial FAS (PFAS) and made up the FAS/PFAS group, 18 were diagnosed as heavily exposed non-syndromal (HE) and 29 were age matched controls. Subjects were scanned at the Cape Universities Body Imaging Centre (CUBIC) located at Groote Schuur Hospital on a 3T Siemens Skyra MRI. Structural images were obtained using the MEMPRAGE sequence. From these images T1, T2, T2* and PD parameter maps were constructed and segmented into 43 regions of interest (ROI) using Freesurfer, FSL and AFNI. Linear regression analyses were used to analyse group differences as well as correlations between parameter values and the amount of alcohol the mother consumed during pregnancy. Results: Significant T1 differences were found in the caudate, cerebellar cortex, hippocampus, accumbens, putamen, choroid plexus, ventral diencephalon (DC), right vessel and ventricles. Significant T2 differences were found in the caudate, brain stem, corpus callosum (CC), amygdala, cerebral cortex, choroid plexus, vessels and ventricles. Significant T2* differences were found in the cerebellar cortex, optic chiasm and ventricles. Significant PD differences were found in the hippocampus and left lateral ventricle. The exploratory nature of this study resulted in none of the results surviving FDR correction for multiple comparisons. Conclusions: Overall, our findings point to regional PAE-related increases in water content and cellular and molecular changes in underlying tissue of the anatomical structure. Exceptions were the right cerebral cortex, brain stem, hippocampus, amygdala and ventral diencephalon where our findings point to less free water and increased cell density, and cerebellar cortex where simultaneous reductions in T1 and T2* suggest the possibility of increased iron content. In highly myelinated white matter structures, such as the CC and optic chiasm, our results point to PAErelated demyelination, and possibly increased iron. These findings extend previous knowledge of effects of PAE and demonstrate that tissues are affected at a microstructural level.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Fetal alcohol spectrum disorder is a disease caused by prenatal alcohol exposure. It is characterized by craniofacial abnormalities, growth retardation, central nervous system defects, learning disabilities and a variety of other minor defects. Even though it affects 2-5% of individuals born every year, very little is known about the mechanisms that cause it. The zebrafish (Danio rerio) presents as an interesting and efficient model for studying this disease. This study provides some insight into the mechanisms underlying observed FASD phenotypes and, more specifically, the transcription factor elf3, which is downregulated in response to ethanol exposure during early embryonic development. Here we show a number of elf3 target genes that are downregulated during early development in response to ethanol exposure. We also give some insight into the expression pattern of elf3 in relation to zygotic genome activation. Translation blocking morpholino oligonucleotides were used to implicate Elf3 in epiboly movements during gastrulation and zebrafish tail development. Taken together these results help to strengthen the zebrafish as a model for FASD in addition to giving greater insight into both the expression pattern and role of Elf3 during development.

Thesis (MA)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Maternal drinking during pregnancy and its consequences are a growing health concern worldwide. It has also been identified as a significant problem in South African communities with some of the highest prevalence rates of Fetal Alcohol Spectrum Disorder (FASD) reported in South Africa. The primary aim of this study was to explore how women in a South African community in the Northern Cape Province perceive the personal and general risk of drinking during pregnancy. The secondary aims were to ascertain whether there was evidence of unrealistic optimism, to examine whether there were personal characteristics that are associated with high or low risk perception, and to examine women‟s knowledge of FASD. A total of 128 women from De Aar in the Northern Cape, an area with a high prevalence of FASD, and therefore drinking during pregnancy, were recruited to take part in the study. Participants had previously taken part in a FASD prevention programme. Questionnaires were administered assessing the perception of the risk posed to a participant‟s own child should she drink during pregnancy, and the risk posed to others‟ children should they drink during pregnancy. The questionnaire also contained questions on FASD knowledge and demographic variables. Participants were between 18 and 44 years of age and reported high rates of unemployment. Most women had more than one child and 7.8% had a child diagnosed with FASD. No evidence for unrealistic optimism was found. Multiple regression analyses revealed both FASD knowledge, and the perception of how easy it would be for oneself to stop drinking, were significant predictors for both personal and general risk. A model including the perception of general risk, FASD knowledge and the perception of how easily one could stop drinking accounted for the most variance in the perception of personal risk (66.4%). Perception of personal risk on its own was the strongest predictor of the perception of general risk accounting for 56.1% of variance. There was no significant correlation between passage of time and FASD knowledge, but possible gaps in FASD knowledge were identified. The study provides an overview of the perception of the risk of drinking during pregnancy in the target population. It also suggests improvements to the research design and materials for further research. / AFRIKAANSE OPSOMMING: Moederlike drankgebruik gedurende swangerskap en die gevolge daarvan word wêreldwyd met groeiende kommer beskou. Dit is ook as ʼn wesenlike probleem in Suid-Afrika geïdentifiseer, met van die hoogste voorkomssyfers van Fetale Alkohol Spektrumafwykings (FASA) wat in Suid-Afrika aangeteken is. Die primêre doel van hierdie studie was om, in ʼn Suid-Afrikaanse gemeenskap in die Noord Kaap provinsie, die persepsie van persoonlike en algemene risiko van drink tydens swangerskap onder vrouens, te ondersoek. Die sekondêre doelstellings was om vas te stel of daar bewyse van onrealistiese optimisme is; te bepaal of daar persoonlike eienskappe is wat korreleer met ʼn hoë of lae risiko-persepsie, en om ook die vroue se kennis van Fetale Alkohol Spektrumafwykings (FASA) te ondersoek. 128 vroue van De Aar in die Noord-Kaap is gewerf om aan die studie deel te neem. Die gebied het 'n hoë FASA voorkoms, en dus ook alkoholgebruik tydens swangerskap. Deelnemers het voorheen deelgeneem aan 'n FASA voorkomingsprogram. Vraelyste is voltooi rakende die persepsie van die risiko vir 'n deelnemer se eie kind sou sy tydens swangerskap drink, en die risiko vir ander se kinders, sou hulle tydens swangerskap drink. Die vraelys het ook vrae oor FASA kennis en demografiese veranderlikes ingesluit. Deelnemers was tussen 18 en 44 jaar oud en het hoë vlakke van werkloosheid gerapporteer. Meeste vrouens het meer as een kind gehad en 7.8% het ʼn kind wat met FASA gediagnoseer is gehad. Geen bewyse vir onrealistiese optimisme is gevind nie. Meervoudige regressie-ontleding het bevind dat beide FASA-kennis en die persepsie van hoe maklik dit vir ‟n deelnemer self sou wees om op te hou drink, beduidende voorspellers vir beide persoonlike en algemene risiko is. 'n Model wat die persepsie van algemene risiko, FASA-kennis en die persepsie van hoe maklik 'n deelnemer self kan ophou drink, het die grootste variansie in die persepsie van persoonlike risiko verduidelik (66,4 %). Persepsie van persoonlike risiko op sy eie, was die sterkste voorspeller van die persepsie van algemene risiko, opsigself verantwoordelik vir 56,1% van die variansie. Daar was geen beduidende korrelasie tussen die verloop van tyd en FASA kennis nie, maar moontlike gapings in die kennis van FASA is geïdentifiseer. Die studie bied 'n oorsig van die persepsie van die risiko van drankgebruik tydens swangerskap in die teikenbevolking. Dit stel ook verbeteringe vir die navorsingsmetodiek voor vir toekomstige navorsing.

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively. Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro model system, the present study assessed the effects of Cr(VI) on T cell functions, as the first step of our investigation of the mechanism underlying Cr(VI)-inhibited immunosurveillance and carcinogenesis. Our results showed that Cr(VI) decreased the viability of CD4+ and CD8+ T cells, inhibited T cell activation, functions, including cytokine release, and degranulation. Fetal ethanol (ETOH) exposure can damage the developing central nervous system and lead to cognitive and behavioral deficits, known as fetal alcohol spectrum disorders (FASD). The use of animal models, especially mouse models is essential for investigating the neurogenetic mechanism of fetal ETOH effects and screening pharmacotherapies against it, due to the extensive knowledge of mouse genetics. However, the availability of mouse model is limited. Via adopting various dosage, timing and administration routes of ETOH exposure, we developed two mouse models to assess behavioral or cognitive changes caused by fetal ETOH exposure in pre-weaning and adolescent period. Our results show that high dosage of ETOH exposure (4 g/kg) during PD 4-10 resulted in hyperactivity, disinhibition, and deficits in learning and memory in mouse offspring, which lays the groundwork for the future FASD research.

The Ph.D. dissertation encompasses an interdisciplinary study exploring qualitative, holistic strategies for individuals with Fetal Alcohol Spectrum Disorder (FASD) in integrated areas of law, medicine, education, psychology and justice, through both inductive analysis of field research as well as through relevant documentary analysis, incorporating a global or comparative component. Compliance with Guidelines for Research Involving Aboriginal Peoples has been sustained through community partnerships with various First Nations and Métis Communities, Elders and Parents, as well as with an FASD Parental Advocacy Group, advised by a team of interdisciplinary researchers in the academy. Accordingly, emergent research protocols were co-constructed through ongoing collaboration with the various community partners. In Aboriginal research, it is essential not to parachute in and out of communities with the data, but rather to forge genuine, collaborative, long term partnerships, and to build capacity in those communities.<p> The dissertation format approved by the Student Advisory Committee is Manuscript Style, a format approved by the University of Saskatchewans College of Graduate Studies and Research (formerly referred to as X-Format) similar to a self-edited book or collection of articles with introduction, sub-text, intra-text and general discussion to link the manuscripts. The various manuscripts comprising the present thesis include:<p> 1.Framing the Research Anthology: A Vision Quest, Ékehohksimoht Ke-kiss-see Muya<p> Section One situates the research style, process, approach, substance and rationale of the dissertation. It is largely situated within holistic Indigenous epistemologies, which may require a paradigm shift, in contrast to more bounded western world views.<p> Interdisciplinary, holistic, community-based research on the topic of FASD, including a search for solutions, extends globally, across the lifespan, and across sectors.<p> II. Indigenous Disadvantage and Despair, An Evaluation of Recent Strategies and Alternatives: Healing and Transformation, Pluralism and Reconciliation, Ne wah kuma ka tik<p> Section Two explores historical and contextual factors leading to a high prevalence of FASD, as well as strategies to overcome disadvantage, including Reconciliation, Treaty Processes, and Research as Reconciliation. Local Narratives are privileged over Meta-narratives, to counter the power of global market forces usurping the sphere of family, community and culture.<p> III. Disjunctures and Discontinuities in the Law of Mental Intent: FASD as a Site of Resistance and Transformation, Esquiskuit<p> Section Three examines the disconnect between medical knowledge of FASD, on the one hand, and the Laws of Mental Intent, on the other, inspiring a search for a unified, integrated theory of mental disorder and criminal responsibility that takes into account modern neurocognitive conditions like FASD. Section Three further explores the present piecemeal and compartmentalized rules for fitness, responsibility, various levels of mental intent, and a resultant rationale, substance and process of law reform and systemic change.<p> IV. FASD and Holistic Literacies: A Talking or Sharing Circle, Wa-sa-cam-e-be-ke-skue<p> Section Fours inductive themes comprise model practice guidelines for the gestalt of Literacy and FASD, derived from inductive analysis of qualitative data collected in the field research. The data was collected using Sharing Circles with Aboriginal Elders, Parents, and Mentors of Individuals with FASD; Conversational Interviews with Parents and Children with FASD; as well as Interviews and Focus Groups with various Professionals who support individuals with FASD and their Families. Special protocols were followed in creating and participating in the Indigenous Research, Sharing Circles and Conversational Interviews. Meta-paradigmatic analysis situates Indigenous Research Methodologies among emerging, multi-disciplinary, inductive methodologies suitable for understanding the infinite complexity of natural phenomena, such as FASD.<p> V. Epilogue: An Honour Song, Kethou-ne-ka-mon<p> Circles of healing, transformation and reconciliation heal wounds, reconcile differences, and transform paradigms of justice, health, education and governance, through the incorporation of models of equitable, holistic relationships with one another and with Mother Earth. Multidisciplinary and cross-cultural perspectives, dialogues between local and global, and particular and universal, become matrices to support new paradigms embodying broader reflections of reality.

The Ph.D. dissertation encompasses an interdisciplinary study exploring qualitative, holistic strategies for individuals with Fetal Alcohol Spectrum Disorder (FASD) in integrated areas of law, medicine, education, psychology and justice, through both inductive analysis of field research as well as through relevant documentary analysis, incorporating a global or comparative component. Compliance with Guidelines for Research Involving Aboriginal Peoples has been sustained through community partnerships with various First Nations and Métis Communities, Elders and Parents, as well as with an FASD Parental Advocacy Group, advised by a team of interdisciplinary researchers in the academy. Accordingly, emergent research protocols were co-constructed through ongoing collaboration with the various community partners. In Aboriginal research, it is essential not to parachute in and out of communities with the data, but rather to forge genuine, collaborative, long term partnerships, and to build capacity in those communities.<p> The dissertation format approved by the Student Advisory Committee is Manuscript Style, a format approved by the University of Saskatchewans College of Graduate Studies and Research (formerly referred to as X-Format) similar to a self-edited book or collection of articles with introduction, sub-text, intra-text and general discussion to link the manuscripts. The various manuscripts comprising the present thesis include:<p> 1.Framing the Research Anthology: A Vision Quest, Ékehohksimoht Ke-kiss-see Muya<p> Section One situates the research style, process, approach, substance and rationale of the dissertation. It is largely situated within holistic Indigenous epistemologies, which may require a paradigm shift, in contrast to more bounded western world views.<p> Interdisciplinary, holistic, community-based research on the topic of FASD, including a search for solutions, extends globally, across the lifespan, and across sectors.<p> II. Indigenous Disadvantage and Despair, An Evaluation of Recent Strategies and Alternatives: Healing and Transformation, Pluralism and Reconciliation, Ne wah kuma ka tik<p> Section Two explores historical and contextual factors leading to a high prevalence of FASD, as well as strategies to overcome disadvantage, including Reconciliation, Treaty Processes, and Research as Reconciliation. Local Narratives are privileged over Meta-narratives, to counter the power of global market forces usurping the sphere of family, community and culture.<p> III. Disjunctures and Discontinuities in the Law of Mental Intent: FASD as a Site of Resistance and Transformation, Esquiskuit<p> Section Three examines the disconnect between medical knowledge of FASD, on the one hand, and the Laws of Mental Intent, on the other, inspiring a search for a unified, integrated theory of mental disorder and criminal responsibility that takes into account modern neurocognitive conditions like FASD. Section Three further explores the present piecemeal and compartmentalized rules for fitness, responsibility, various levels of mental intent, and a resultant rationale, substance and process of law reform and systemic change.<p> IV. FASD and Holistic Literacies: A Talking or Sharing Circle, Wa-sa-cam-e-be-ke-skue<p> Section Fours inductive themes comprise model practice guidelines for the gestalt of Literacy and FASD, derived from inductive analysis of qualitative data collected in the field research. The data was collected using Sharing Circles with Aboriginal Elders, Parents, and Mentors of Individuals with FASD; Conversational Interviews with Parents and Children with FASD; as well as Interviews and Focus Groups with various Professionals who support individuals with FASD and their Families. Special protocols were followed in creating and participating in the Indigenous Research, Sharing Circles and Conversational Interviews. Meta-paradigmatic analysis situates Indigenous Research Methodologies among emerging, multi-disciplinary, inductive methodologies suitable for understanding the infinite complexity of natural phenomena, such as FASD.<p> V. Epilogue: An Honour Song, Kethou-ne-ka-mon<p> Circles of healing, transformation and reconciliation heal wounds, reconcile differences, and transform paradigms of justice, health, education and governance, through the incorporation of models of equitable, holistic relationships with one another and with Mother Earth. Multidisciplinary and cross-cultural perspectives, dialogues between local and global, and particular and universal, become matrices to support new paradigms embodying broader reflections of reality.

Despite the anecdotal evidence of social difficulties in children with Fetal Alcohol Spectrum Disorders (FASD), and the risk for secondary disabilities as a result of these social difficulties, very little research has examined social-emotional functioning in children with FASD. The majority of the research conducted thus far has relied on parent and teacher reports to document social impairments. These parent and teacher reports provide a broad measure of social functioning but are unable to elucidate the specific aspects of social functioning that this group of children might find difficult. As a result, it has been very difficult to develop effective social interventions for children with FASD because it is unclear what aspects of social functioning should be targeted. The current study aimed to examine emotion recognition abilities in children with FASD, as recognition of emotions is an important precursor for appropriate social interaction. The study included 22 participants with diagnosed FASD (ages 8-14), with age- and gender- matched typically developing controls. Participants were assessed using computerized measures of emotion recognition from three nonlinguistic modalities: facial expressions (static and dynamic, child and adult faces), emotional tone of voice (child and adult voices), and body positioning and movement (postures and point-light walkers). In addition, participants completed a task assessing emotion recognition in real-life scenarios. Finally, caregivers completed measures of behavioural functioning, adaptive functioning, FASD symptomatology, and a demographics questionnaire. Overall, findings suggest that children with FASD do have more difficulties than age-matched typically developing peers in aspects of emotion recognition, with particular difficulties in recognizing emotions from adult facial expressions and adult emotional prosody. In addition, children with FASD had more difficulty perceiving differences in facial expressions. When the effect of age was examined, it was found that some aspects of emotion recognition were more impaired in children with FASD between age eight and ten years compared to same-age typically developing peers and compared to children with FASD age 11-14. This finding suggests that younger children with FASD may demonstrate a delay in the acquisition of some aspects of emotion recognition or may be more vulnerable to the information processing demands of some tasks compared to older children with FASD. The types of emotion recognition difficulties found in the current study supported a pattern where children with FASD make more errors on emotion recognition tasks when the complexity of the task is increased and consequently demands greater information processing. As such, it is anticipated that children with FASD would be likely to have the most difficulty with emotion recognition abilities embedded within complex, rapidly changing, real-world social situations, and in recognizing more subtle emotional displays. Caregivers, teachers, and professionals living and working with children and youth with FASD should be aware of possible emotion recognition difficulties in complex social situations and should help foster stronger emotion recognition skills when difficulties are detected.

Despite the anecdotal evidence of social difficulties in children with Fetal Alcohol Spectrum Disorders (FASD), and the risk for secondary disabilities as a result of these social difficulties, very little research has examined social-emotional functioning in children with FASD. The majority of the research conducted thus far has relied on parent and teacher reports to document social impairments. These parent and teacher reports provide a broad measure of social functioning but are unable to elucidate the specific aspects of social functioning that this group of children might find difficult. As a result, it has been very difficult to develop effective social interventions for children with FASD because it is unclear what aspects of social functioning should be targeted. The current study aimed to examine emotion recognition abilities in children with FASD, as recognition of emotions is an important precursor for appropriate social interaction. The study included 22 participants with diagnosed FASD (ages 8-14), with age- and gender- matched typically developing controls. Participants were assessed using computerized measures of emotion recognition from three nonlinguistic modalities: facial expressions (static and dynamic, child and adult faces), emotional tone of voice (child and adult voices), and body positioning and movement (postures and point-light walkers). In addition, participants completed a task assessing emotion recognition in real-life scenarios. Finally, caregivers completed measures of behavioural functioning, adaptive functioning, FASD symptomatology, and a demographics questionnaire. Overall, findings suggest that children with FASD do have more difficulties than age-matched typically developing peers in aspects of emotion recognition, with particular difficulties in recognizing emotions from adult facial expressions and adult emotional prosody. In addition, children with FASD had more difficulty perceiving differences in facial expressions. When the effect of age was examined, it was found that some aspects of emotion recognition were more impaired in children with FASD between age eight and ten years compared to same-age typically developing peers and compared to children with FASD age 11-14. This finding suggests that younger children with FASD may demonstrate a delay in the acquisition of some aspects of emotion recognition or may be more vulnerable to the information processing demands of some tasks compared to older children with FASD. The types of emotion recognition difficulties found in the current study supported a pattern where children with FASD make more errors on emotion recognition tasks when the complexity of the task is increased and consequently demands greater information processing. As such, it is anticipated that children with FASD would be likely to have the most difficulty with emotion recognition abilities embedded within complex, rapidly changing, real-world social situations, and in recognizing more subtle emotional displays. Caregivers, teachers, and professionals living and working with children and youth with FASD should be aware of possible emotion recognition difficulties in complex social situations and should help foster stronger emotion recognition skills when difficulties are detected.